Purpose We examined the effects of Positive Action (PA), a school-based social-emotional learning and health promotion program, on the emotional health of predominately low-income and ethnic minority urban youth. Methods The study was a matched-pair, cluster-randomized controlled trial involving 14 Chicago public schools. Outcomes were assessed over a 6-year period of program implementation for a cohort of youth in each school, followed from grades 3 to 8. Youth reported on their emotional health (positive affect, life satisfaction, depression, anxiety) and social-emotional and character development. Growth-curve and structural-equation modeling analyses assessed overall program effects on the emotional health outcomes as well as mediation of these effects via the program's impact on youths' social-emotional and character development. Results Students in PA schools, compared with those in control schools, had more favorable change over the course of the study in positive affect (standardized mean difference effect size [ES] = .17) and life satisfaction (ES = .13) as well as significantly lower depression (ES = −.14) and anxiety (ES = −.26) at study end point. Program effects for positive affect, depression, and anxiety were mediated by more favorable change over time in social-emotional and character development for students in PA schools. Conclusions Results suggest that universal, school-based programs can benefit the emotional health of youth in low-income, urban settings. The modest magnitude of effects over an extended period of program implementation, however, reflects the challenges of both mounting interventions and offsetting formidable risks for mental health problems in such environments.